DESCRIPTION(From applicant's abstract): The principal investigator has been a leader in the characterization of opioid receptor structure and function for almost 40 years. Recently, the specific aims have taken a combined biochemical and molecular approach to examining important structural components that are responsible for regulation of mu and delta receptors. There are four major specific aims in the next funding period. Aim 1 will explore posttranslational modifications of mu receptors, focusing on locations of glycosylation sites, phosphorylation sites, disulfide bridges and cysteine residues involved in receptor palmitoylation. Aim 2 will examine the role of cytoskeletal elements in regulating opioid receptor binding and G-protein activation. These will build on yeast two hybrid results which suggest that proteins like filamin and actinin interact with mu receptors, and will utilize various reagents which interfere with cytoskeletal function to affect opioid receptor parameters. Aim 3 will explore the role of tyrosine phosphorylation in regulating mu opioid receptor function and internalization. Aim 4 will examine the identities of transcription factors that affect the promoter of the mu receptor gene.